Warning:

This document is being maintained for historical purposes, but is now out of date. To view current guidelines please visit:

• STD Treatment Guidelines   at http://www.cdc.gov/STD/treatment

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1993 Sexually Transmitted Diseases Treatment Guidelines

09/24/1993

SUGGESTED CITATION
Centers for Disease Control and Prevention. 1993 Sexually
transmitted diseases treatment guidelines. MMWR 1993;42(No. RR-14):
{inclusive page numbers}.

CIO Responsible for this publication:
National Center for Prevention Services,
Division of Sexually Transmitted Diseases and HIV Prevention

HUMAN PAPILLOMAVIRUS INFECTION

Genital Warts
     
     Exophytic genital and anal warts are benign growths most
commonly caused by HPV types 6 or 11. Other types that may be
present in the anogenital region (e.g., types 16, 18, 31, 33, and
35) have been strongly associated with genital dysplasia and
carcinoma. These types are usually associated with subclinical
infection, but occasionally are found in exophytic warts.

Treatment
     The goal of treatment is removal of exophytic warts and the
amelioration of signs and symptoms -- not the eradication of HPV.
No therapy has been shown to eradicate HPV. HPV has been identified
in adjacent tissue after laser treatment of HPV- associated
cervical intraepithelial neoplasia and after attempts to eliminate
subclinical HPV by extensive laser vaporization of the anogenital
area.

     Genital warts are generally benign growths that cause minor or
no symptoms aside from their cosmetic appearance. Treatment of
external genital warts is not likely to influence the development
of cervical cancer. A multitude of randomized clinical trials and
other treatment studies have demonstrated that currently available
therapeutic methods are 22%-94% effective in clearing external
exophytic genital warts, and that recurrence rates are high
(usually at least 25% within 3 months) with all modalities. Several
well-designed studies have indicated that treatment is more
successful for genital warts that are small and that have been
present less than 1 year. No studies have assessed if treatment of
exophytic warts reduces transmission of HPV. Many experts speculate
that exophytic warts may be more infectious than subclinical
infection, and therefore, the risk for transmission might be
reduced by "debulking" genital warts. Most experts agree that
recurrences of genital warts more commonly result from reactivation
of subclinical infection than reinfection by a sex partner. The
effect of treatment on the natural history of HPV is unknown. If
left untreated, genital warts may resolve on their own, remain
unchanged, or grow. In placebo-controlled studies, genital warts
have cleared spontaneously without treatment in 20%-30% of patients
within 3 months.

Regimens -
     Treatment of genital warts should be guided by the preference
of the patient. Expensive therapies, toxic therapies, and
procedures that result in scarring should be avoided. A specific
treatment regimen should be chosen with consideration given to
anatomic site, size, and number of warts as well as the expense,
efficacy, convenience, and potential for adverse effects. Extensive
or refractory disease should be referred to an expert.

     Carbon dioxide laser and conventional surgery are useful in
the management of extensive warts, particularly for those patients
who have not responded to other regimens; these alternatives are
not appropriate for treatment of limited lesions. One randomized
trial of laser therapy indicated efficacy of 43%, with recurrence
among 95% of patients. A randomized trial of surgical excision
demonstrated efficacy of 93%, with recurrences among 29% of
patients. These therapies and more cost-effective treatments do not
eliminate HPV infection.

     Interferon therapy is not recommended because of its cost and
its association with a high frequency of adverse side effects, and
efficacy is no greater than that of other available therapies. Two
randomized trials established systemic interferon alpha to be no
more effective than placebo. Efficacy of interferon injected
directly into genital warts (intralesional therapy) during two
randomized trials was 44%-61%, with recurrences among none to 67%
of patients.

     Therapy with 5-fluorouracil cream has not been evaluated in
controlled studies, frequently causes local irritation, and is not
recommended for the treatment of genital warts.

External Genital/Perianal Warts
     Cryotherapy with liquid nitrogen or cryoprobe.
                       or
     Podofilox 0.5% solution for self-treatment (genital warts
     only). Patients may apply podofilox with a cotton swab to warts
     twice daily for 3 days, followed by 4 days of no therapy. This
     cycle may be repeated as necessary for a total of 4 cycles. Total
     wart area treated should not exceed 10 cm2, and total volume of
     podofilox should not exceed 0.5 mL per day. The health-care
     provider should demonstrate the proper application technique and
     identify which warts should be treated. If possible, the
     health-care provider should apply the initial treatment to
     demonstrate the proper application technique and identify which
     warts should be treated. The use of podofilox is contraindicated
     during pregnancy.
                       or
     Podophyllin 10%-25%, in compound tincture of benzoin. To avoid
     the possibility of problems with systemic absorption and toxicity,
     some experts recommend that application be limited to less than or
     equal to 0.5 mL or less than or equal to 10 cm2 per session.
     Thoroughly wash off in 1-4 hours. Repeat weekly if necessary. If
     warts persist after six applications, other therapeutic methods
     should be considered. The use of podophyllin is contraindicated
     during pregnancy.
                       or
     Trichloroacetic acid (TCA) 80%-90%. Apply only to warts;
     powder with talc or sodium bicarbonate (baking soda) to remove
     unreacted acid. Repeat weekly if necessary. If warts persist after
     six applications, other therapies should be considered.
                       or
     Electrodesiccation or electrocautery. Electrodesiccation and
     electrocautery are contraindicated for patients with cardiac
     pacemakers or for lesions proximal to the anal verge.

     Cryotherapy is relatively inexpensive, does not require
anesthesia, and does not result in scarring if performed properly.
Special equipment is required, and most patients experience
moderate pain during and after the procedure. Efficacy during four
randomized trials was 63%-88%, with recurrences among 21%-39% of
patients.

     Therapy with 0.5% podofilox solution is relatively
inexpensive, simple to use, safe, and is self-applied by patients
at home. Unlike podophyllin, podofilox is a pure compound with a
stable shelf-life and does not need to be washed off. Most patients
experience mild/moderate pain or local irritation after treatment.
Heavily keratinized warts may not respond as well as those on moist
mucosal surfaces. To apply the podofilox solution safely and
effectively, the patient must be able to see and reach the warts
easily. Efficacy during five recent randomized trials was 45%-88%,
with recurrences among 33%-60% of patients.

     Podophyllin therapy is relatively inexpensive, simple to use,
and safe. Compared with other available therapies, a larger number
of treatments may be required. Most patients experience mild to
moderate pain or local irritation after treatment. Heavily
keratinized warts may not respond as well as those on moist mucosal
surfaces. Efficacy in four recent randomized trials was 32%-79%,
with recurrences among 27%-65% of patients.

     Few data on the efficacy of TCA are available. One randomized
trial among men demonstrated 81% efficacy and recurrence among 36%
of patients; the frequency of adverse reactions was similar to that
seen with the use of cryotherapy. One study among women showed
efficacy and frequency of patient discomfort to be similar to
podophyllin. No data on the efficacy of bichloroacetic acid are
available.

     Few data on the efficacy of electrodesiccation are available.
One randomized trial of electrodesiccation demonstrated an efficacy
of 94%, with recurrences among 22% of patients; another randomized
trial of diathermocoagulation demonstrated an efficacy of 35%.
Local anesthesia is required, and patient discomfort is usually
moderate.

Cervical Warts
     For women with (exophytic) cervical warts, dysplasia must be
excluded before treatment is begun. Management should be carried
out in consultation with an expert.

Vaginal Warts
     Cryotherapy with liquid nitrogen. The use of a cryoprobe in
     the vagina is not recommended because of the risk for vaginal
     perforation and fistula formation.
                              or
     TCA 80%-90%. Apply only to warts; powder with talc or sodium
     bicarbonate (baking soda) to remove unreacted acid. Repeat weekly
     as necessary. If warts persist after six applications, other
     therapeutic methods should be considered.
                              or
     Podophyllin 10%-25% in compound tincture of benzoin. Apply to
     the treatment area, which must be dry before removing the speculum.
     Treat less than or equal to 2 cm2 per session. Repeat application
     at weekly intervals. Because of concern about potential systemic
     absorption, some experts caution against vaginal application of
     podophyllin. The use of podophyllin is contraindicated during
     pregnancy.

Urethral Meatus Warts
     Cryotherapy with liquid nitrogen.
                   or
     Podophyllin 10%-25% in compound tincture of benzoin. The
     treatment area must be dry before contact with normal mucosa.
     Podophyllin must be washed off in 1-2 hours. Repeat weekly if
     necessary. If warts persist after six applications, other
     therapeutic methods should be considered. The use of podophyllin is
     contraindicated during pregnancy.

Anal Warts
     Cryotherapy with liquid nitrogen.
                        or
     TCA 80%-90%. Apply only to warts; powder with talc or sodium
     bicarbonate (baking soda) to remove unreacted acid. Repeat weekly
     if necessary. If warts persist after six applications, other
     therapeutic methods should be considered.
                        or
     Surgical removal.

NOTE: Management of warts on rectal mucosa should be referred
to an expert.

Oral Warts
     Cryotherapy with liquid nitrogen
                    or
     Electrodesiccation or electrocautery
                    or
     Surgical removal.

Follow-Up
     After warts have responded to therapy, follow-up is not
necessary. Annual cytologic screening is recommended for women with
or without genital warts. The presence of genital warts is not an
indication for colposcopy.

Management of Sex Partners
     Examination of sex partners is not necessary for management of
genital warts because the role of reinfection is probably minimal.
Many sex partners have obvious exophytic warts and may desire
treatment; also, partners may benefit from counseling. Patients
with exophytic anogenital warts should be made aware that they are
contagious to uninfected sex partners. The majority of partners,
however, are probably already subclinically infected with HPV, even
if they do not have visible warts. No practical screening tests for
subclinical infection are available. Even after removal of warts,
patients may harbor HPV in surrounding normal tissue, as may
persons without exophytic warts. The use of condoms may reduce
transmission to partners likely to be uninfected, such as new
partners; however, the period of communicability is unknown.
Experts speculate that HPV infection may persist throughout a
patient's lifetime in a dormant state and become infectious
intermittently. Whether patients with subclinical HPV infection are
as contagious as patients with exophytic warts is unknown.

Special Considerations

Pregnancy -
The use of podophyllin and podofilox are contraindicated during
pregnancy. Genital papillary lesions have a tendency to proliferate
and to become friable during pregnancy. Many experts advocate
removal of visible warts during pregnancy.

     HPV types 6 and 11 can cause laryngeal papillomatosis among
infants. The route of transmission (transplacental, birth canal, or
postnatal) is unknown, and laryngeal papillomatosis has occurred
among infants delivered by caesarean section. Hence, the preventive
value of caesarean delivery is unknown. Caesarean delivery must not
be performed solely to prevent transmission of HPV infection to the
newborn. However, in rare instances, caesarean delivery may be
indicated for women with genital warts if the pelvic outlet is
obstructed or if vaginal delivery would result in excessive
bleeding.

HIV Infection -
     Persons infected with HIV may not respond to therapy for HPV
as well as persons without HIV.

Subclinical Genital HPV Infection (Without Exophytic Warts)
     
     Subclinical genital HPV infection is much more common than
exophytic warts among both men and women. Infection is often
indirectly diagnosed on the cervix by Pap smear, colposcopy, or
biopsy and on the penis, vulva, and other genital skin by the
appearance of white areas after application of acetic acid.
Acetowhitening is not a specific test for HPV infection, and
false-positive tests are common. Definitive diagnosis of HPV
infection relies on detection of viral nucleic acid (DNA or RNA) or
capsid proteins. Pap smear diagnosis of HPV generally does not
correlate well with detection of HPV DNA in cervical cells. Cell
changes attributed to HPV in the cervix are similar to those of
mild dysplasia and often regress spontaneously without treatment.
Tests for the detection of several types of HPV DNA in cells
scraped from the cervix are now widely available, but the clinical
utility of these tests for managing patients is not known.
Management decisions should not be made on the basis of HPV DNA
tests. Screening for subclinical genital HPV infection using DNA
tests or acetic acid is not recommended.

Treatment
     
     In the absence of coexistent dysplasia, treatment is not
recommended for subclinical genital HPV infection diagnosed by Pap
smear, colposcopy, biopsy, acetic acid soaking of genital skin or
mucous membranes, or the detection of HPV nucleic acids (DNA or
RNA) or capsid antigen, because diagnosis often is questionable and
no therapy has been demonstrated to eradicate infection. HPV has
been demonstrated in adjacent tissue after laser treatment of
HPV-associated dysplasia and after attempts to eliminate
subclinical HPV by extensive laser vaporization of the anogenital
area of men and women.

     In the presence of coexistent dysplasia, management should be
based on the grade of dysplasia.

Management of Sex Partners
     
     Examination of sex partners is not necessary. The majority of
partners are probably already infected subclinically with HPV. No
practical screening tests for subclinical infection are available.
The use of condoms may reduce transmission to partners likely to be
uninfected, such as new partners; however, the period of
communicability is unknown. Experts speculate that HPV infection
may persist throughout a patient's lifetime in a dormant state and
become infectious intermittently. Whether patients with subclinical
HPV infection are as contagious as patients with exophytic warts is
unknown.

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